Neuroscience and Endocrinology

Objectives

• Goals are to define the ANS role, compare somatic and ANS roles, differentiate parasympathetic and sympathetic nervous system functions.
• It also includes stating the effects of parasympathetic and sympathetic divisions on organ systems like the cardiovascular system, GI system, lungs, and genitalia.

Autonomic Nervous System Overview

• The motor system has two systems: the somatic controlling skeletal muscles and the autonomic controlling physiological characteristics such as blood pressure, heart rate, respiratory rate, digestion, and sweating.
• Neurons of the autonomic system, like somatic motor neurons, are in the spinal cord and brainstem, and release acetylcholine neurotransmitter.

Autonomic Neurons

• Autonomic motor neurons are in the lateral horn rather than ventral horns.
• Autonomic neurons do not directly project to muscles, but synapse in a ganglion outside the CNS.
• These are called preganglionic neurons.
• A second motor neuron, the postganglionic neuron, projects to the muscle.
• No autonomic neurons exist in the cervical spinal cord.

Autonomic Subdivisions

• The autonomic nervous system has two subdivisions: the sympathetic and parasympathetic divisions.

Sympathetic Branch

• Main function is control of the "flight or fight" response, charged with responding to emergencies.
• Sympathetic effects include increased heart rate, BP, and sweating, leading to dry mouth as adrenaline rush symptom.
• Preganglionic neurons are in the thoracic and first two lumbar segments of the spinal cord, secreting acetylcholine and synapsing with postganglionic neurons in sympathetic ganglia.
• Ganglia form chain-like structures parallel to the spinal cord (paravertebral ganglia), where neurons release norepinephrine neurotransmitter.
• The sympathetic system stimulates the adrenal glands to release the hormone epinephrine that causes the adrenaline rush.

Parasympathetic Branch

• Often called “resting and digesting" and has the opposite effect of the sympathetic division.
• It is responsible for everyday activities and reversing sympathetic effects.
• Leads to decreased heart rate, respiration, and blood pressure, and increased digestive activity such as salivation and stomach activity.
• Neurons are in the brain stem and the sacral spinal cord and acetylcholine neurotransmitter is released by postganglionic neurons.

Visceral Nervous system

• It contains motor fibers to smooth muscles, modified cardiac muscle fibers, and glandular cells.
• It's organized into sympathetic and parasympathetic components, with sympathetic being thoracolumbar and parasympathetic being craniosacral.
• Consists series of two multipolar neurons.
• Presynaptic neurons are in the gray matter of the CNS
• Postsynaptic neurons are in the PNS.
• Parasympathetic effects are short-lived and highly localized, while sympathetic fibers have diffused and are interconnected.

Anatomical Differences

• Presynaptic cell bodies' location: Sympathetic in intermediolateral cell column (lateral horns) with Parasympathetic in gray matter of the brainstem and sacral segments S2-4
• Functionally: Sympathetic uses NE neurotransmitter other than at sweat glands and Parasympathetic uses ACh neurotransmitter.

Sympathetic Specifics

• Presynaptic cell bodies are in the gray matter of the spinal cord from T1-L2 or L3.
• Postsynaptic cell bodies exist in paravertebral and prevertebral ganglia.
• The pathway includes leaving through Anterior Roots into anterior rami, passing into the sympathetic nervous trunks through the white rami communicantes, and follows one of four potential pathways.
• Pathways include ascend, descend, synapse immediately or bypass the trunk and use the splanchnic nerve.
• Main effects of stimulation include blood vessel contraction, pilomotion (via arrector muscles), sweating and eye dilation.

Sympathetic cell Topography

• Eye, heart, lung and other prevertebral ganglia and associated nerves originate between spinal levels T1 to L2(3)
• Postsynaptic fibers course through various nerves to reach target organs.

Adrenal Medulla

• Sympathetic activation causes the adrenal medulla to release epinephrine and norepinephrine.

Parasympathetic Specifics

• Cranial parasympathetic outflow includes presynaptic neurons are in the gray matter of the brain stem
• Fibers exit cranial nerves: CNIII, CNVII, CNIX, CNX
• Sacral outflow happens withneurons in the gray matter of sacral segments S2-4
• Which exits via anterior roots of spinal nerves S2-4 and pelvic splanic nerves through anterior rami.

ANS Function and the Hypothalamus

• Sympathetic division expends energy, enables stress handling and causes a fight or flight response.
• Parasympathetic division conserves anabolic energy and maintains homeostasis.
• The hypothalamus works with the limbic system but not at the conscious level.
• The reticular formation coordinates heart activity, blood pressure, body temperature, water balance and endocrine activity while responding to stress and fear.
• The brainstem assists with reflexive regulation of heart rate.

Neurotransmitters and Adrenal Hormones

• Cholinergic neurotransmitters, ALL ANS preganglionic and ALL parasympathetic postganglionic neurons, use Acetylcholine
• Nicotinic receptors using Acetylcholine are always stimulatory while Muscarinic are excitatory in Smooth muscle but inhibitory in cardiac muscle.
• Adrenergic, sympathetic neurotransmitter other than at sweat glands, uses NE.
• Alpha receptors from NE use constriction of blood vessels and sphincters and dilation (Alpha1) and inhibits insulin secretion (Alpha2).
• Beta receptors from NE incease the HR and force of contraction (Beta1), Dilates blood vessels and bronchioles (Beta2) and stimulates Lipolysis (Beta3).

Adrenal Gland Basics

• Steroid hormones including glucocorticoids, mineralocorticoids, and adrenal androgens. produced by the cortex
• Catecholamines, epinephrine, and norepinephrine are created by the medulla.
• Rule of thumb: "The deeper you go, the sweeter you get." with Glomerulosa: produces Salt (mineralocorticoids), Fasciculata: produces Sugar (cortisol) and Retcularis: produces Sex hormones (androgens).

Adrenal Hormones

• Aldosterone is the main mineralocorticoid, acting on the kidney to increase sodium reabsorption, potassium excretion, and blood pressure.
• Cortisol is the major glucocorticoid, increasing in stress and maintaining/increasing blood sure
• Androgens, including DHEA, require gonadal conversion to active sex steroids. They also support circulating testosterone in females and males, and help with puberty.
• Epinephrine and norepinephrine activate the sympathetic nervous system, increasing blood pressure and activating glycogenolysis for increased serum glucose by activating glycogenolysis.
• Cortisol is known as body's stress hormone.
• Loss of its regulation leads to cortisol excess/deficiency disorders, such as Cushing syndrome/Addison disease.
• Cortisol also suppresses immunity while increasing gluconeogenesis, decreasing peripheral glucose uptake, and opposing insulin which thus increasing serum glucose
• Excess inhibits growth through muscle atrophy, increased bone resorption, and thinning skin. It also leading to muscle atrophy, increased bone resorption, and thinning of the skin.
• Acutely, it provides energy to stay alert with its catabolic functions, when released from the adrenal cortex. However, this leads to an unmodulated inflammatory response to unrecognized proteins , and psychological stressors.
• Such long-term stress is implicated in diseases such as osteoporosis, rheumatoid arthritis, myopathy, fibromyalgia, chronic fatigue syndrome, chronic pelvic pain, and temporomandibular joint dysfunction.
• Stress-induced signs and symptoms: bone/muscle breakdown, fatigue, depression, sodium/potassium dysregulation, memory impairments, orthostatic hypotension and impaired pupillary light reflex

HPA Axis

• An immune Response will apoptose, meaning that proinflammatory T cells will suppress B cell antibody production and reduce neutrophil migration during inflammation.
• In response to stress, the amygdala sends a signal to the hypothalamus where adrenal glands will release catecholamines, like epinephrine.
• The HPA axis activates and then the adrenal cortex releases cortisol allowing increased blood glucose availability in a catabolic process.

Action Potentials and Electrical Properties

• Neurons and muscle types and some gland cells are excitable; carry an electrical charge at rest and generate tiny currents by permeability changes.
• Action potentials, or nerve impulses, allow signal travel for cell-to-cell communication.
• Cells at rest have a negative charge (resting potential) known as polarized.
• When stimulated, cells become positive and depolarized (less negative).
• Stimulation leads to open sodium gates, travel of sodium across the cell membrane, cell's positive charge, and depolarization (positive feedback loop)
• Repolarization then happens when sodium gates close while the cell opens gates for positively charged potassium to leave (negative feedback loop)
• When the cell becomes more negative when resting, hyperpolarization occurs.
• The action potential thus encompasses depolarization, repolarization, and hyperpolarization.
• Refractory periods are how cells cannot accept another stimulus.
• Electrical potential is possible by different ion distributions and has four channels including leak, modality gated in sensory nerves, ligand gated on neurotransmitters and voltage gated in action potential propagation.
• The resting membrane potential is about -70 mV, maintained by the Na/K Pump.
• Local potentials have sensory conduction, action potential occur from start to finish in All or none manner with high speed due to myelination.

Nerve Function

• Nerve function starts with the Resting Potential which is maintained by NA+/K+ pump
• There is then a Depolarization that triggers Voltage-gated Na+ channels
• Repolarisation is then caused by activation of Voltage-gated K+ channels
• Which is followed by a return the the resting state with NA+/K+ pump activation

Action Potential Propagation

• Speed relies on axon diameter, with saltatory conduction of myelin to speed transmission.

Synapses

• Chemical synapses activate axon terminals and depolarize them, causing calcium gates to open and calcium to flow into the cell.
• Tiny sacs in the terminal (vesicles) then release neurotransmitters, signals that send information to the next cell.
• These Neurotransmitters bind to the cell, opening or closing gates to excite or calm.
• Clean up then occurs, removing the neurotransmitter from the synapse.

Neuromuscular Junction

• This chemical synapse creates a specialized connection between somatic (voluntary) motor neurons and innervated skeletal muscles.
• Surface of muscles is studded with ligand gated sodium channels.
• Which open or close when a molecule, Acetylcholine , binds to the skeletal muscle, opening sodium channels and causing the muscle to depolarize and contract.
• Acetylcholinesterase enzyme is then used for cleaning synapse.

Electrical Synapses

• Special gap junctions help electrical synapses in information transmission freely. These connections can exist between any types of excitable cells in intercalated discs between cardiac muscle fibers.

Neurotransmitters

• Are a language of nervous system
• 50 or more have been identified and most neurons make two or more.
• They influence depending on stimulation frequency and chemical properties.

Neurotransmitter Breakdown

• Chemical structures: Acetylcholine, Biogenic amines (catecholamines and indolamines), Amino acids, Peptides and Puruines and gases/lipids.
• Diversity of functions include excitatory versus inhibitory effects including direct actions on receptor or indirect actions on cell with G-coupling.
• Neuromodulators can be released and local to alter post-synaptic cell sensitivity.
• Channel-linked receptors use ligand-gated ion channels to effect function - the channels for smaller cations such as NA+ influx.
• G protein linked receptors uses transmembrane protein complexes with responses that are indirect, complex, slow, and often occur to cause metabolic changes.
• Mechanism: Neurotransmitter binds to activating G protein. These control the Second messenger production to open / close ion channels, active kinase enzymes or genes for protein production
• G protein signalling mechanism operate, via receptor, to produce adenylate cyclase with ATP that results in cAMP. that results in a change in membrane permeability via opening or closing ion channels.

Questions cover neuron membrane potential, repolarization, refractory period, depolarization, and hyperpolarization. Additionally, the metabolic changes would most likely be observed in a patient with Cushing's syndrome and the primary mechanism by which epinephrine contributes to the fight-or-flight response.